Timing of Levothyroxine Administration Affects Serum Thyrotropin Concentration

CONTEXT: Patients treated with levothyroxine typically ingest it in a fasting state to prevent food impairing its absorption. The serum thyrotropin concentration is the therapeutic index of levothyroxine action. OBJECTIVE: The study objective was to determine the effect of the timing of levothyroxine administration in relationship to food on serum thyrotropin levels. DESIGN: Participants were randomized to one of six sequences, each consisting of three 8-wk regimens in a three-period crossover design. These regimens were in a fasting state, at bedtime, and with breakfast. The concentrations of TSH, free T(4), and total T(3) during each of the three timing regimens were documented. The primary outcome was the difference between serum TSH concentrations under fasting conditions compared with concentrations during the other 8-wk regimens. SETTING: The study was conducted in an academic medical center. PARTICIPANTS: Study participants were receiving levothyroxine for treatment of hypothyroidism or thyroid cancer. RESULTS: Sixty-five patients completed the study. The mean thyrotropin concentration was 1.06 +/- 1.23 mIU/liter when levothyroxine was administered in the fasting state. When levothyroxine was taken with breakfast, the serum thyrotropin concentration was significantly higher (2.93 +/- 3.29 mIU/liter). When levothyroxine was taken at bedtime, the serum TSH concentration was also significantly higher (2.19 +/- 2.66 mIU/liter). CONCLUSION: Nonfasting regimens of levothyroxine administration are associated with higher and more variable serum TSH concentrations. If a specific serum TSH goal is desired, thereby avoiding iatrogenic subclinical thyroid disease, then fasting ingestion of levothyroxine ensures that TSH concentrations remain within the narrowest target range.